Protein, a hydrophilic polymer constituting the living body, has various excellent functions, including biocompatibility and bioactivity such as enzymatic action.
When a protein alone is used as a material, it fails to fully exhibit its excellent functions, because its stability, mechanical strength and workability are low. To compensate for these drawbacks, formation of a conjugate of protein with a synthetic polymer has been intensively studied.
However, it is actually very difficult for a synthetic polymer to form a conjugate with a hydrophilic protein, because the synthetic polymer is usually hydrophobic. As an approach to this problem, it may be possible to utilize a large number of active side chains present in a protein, but protein-based graft polymerization of a monomer requires the use of an aqueous solvent because the reactivity in an organic solvent is poor. Therefore this kind of polymerization has a limit in itself.
With this in mind, the present inventors previously developed a moisture absorbing/releasing material, wherein a small amount of natural polymer is bound to a synthetic polymer by milling gelatin to a fine powder and mechanically kneading the powder in the absence of a solvent. However, its function was subject to limitation because this method is limited to the process for producing a conjugate based on a synthetic polymer.
However, if the content ratio of the protein and synthetic polymer, which are mutually bound, can be freely adjusted and if free shaping is possible, development of various conjugates with never before obtained functions will be possible.
For example, if it is possible to make a highly hydrophilic protein form a conjugate with a synthetic polymer, its affinity to other synthetic polymers becomes high. This not only permits the combined use with other synthetic polymers, but also offers a useful material of good touch or "a moist touch." To achieve this, a design of proteins with high reactivity even in organic solvents is required.
With these circumstances in mind, the present inventors intensively investigated obtaining a protein that is highly reactive in organic solvents.
Although esterification of a compound containing no functional group other than the hydroxyl group, such as a monohydric alcohol, with protein is well known, protein esterification with an alcohol having a functional group other than the hydroxyl group remains yet to be fully clarified.
Directing their attention to the conventional method for esterification of a protein with a monohydric alcohol, the inventors esterified the carboxyl group of protein with a polyfunctional alcohol, and examined the improvement in the reactivity of the protein ester in organic solvents.
As a result, the present inventors found that polyfunctional alcohols, like monohydric alcohols, can be easily esterified with the carboxyl group of a protein, even in the absence of a catalyst, and further that this ester can be used to obtain a protein-synthetic polymer conjugate.